Abstract

The objective of this competitive renewal application is to define the biochemical events that mediate the effects of tyrosine protein kinases on cell growth and metabolism. The proposed studies will focus on a tyrosine kinase signaling paradigm that lead to the activation of pp90 rsk (Rsk) in Xenopus oocytes and eggs. Previous work funded by this grant have led to the identification of the MAP kinase/Rsk pathway in Xenopus oocytes. In the current application, the investigator proposes to build on these findings in order to explore the mechanisms by which this pathway exerts control on oocyte maturation. The project has three specific aims.
Aim 1 proposes to purify, clone, and characterize protein kinases that phosphorylate and activate Rsk.
Aim 2 proposes to investigate the mechanism of activation of Rsk by multi-site phosphorylation mediated by multiple kinases.
Aim 3 proposes to determine the mechanisms of inhibition of MAP kinase activation by cAMP.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK028353-19
Application #
6177116
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Blondel, Olivier
Project Start
1981-03-01
Project End
2002-02-14
Budget Start
2000-07-01
Budget End
2002-02-14
Support Year
19
Fiscal Year
2000
Total Cost
$189,423
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Pharmacology
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Silverman, Eran; Frodin, Morten; Gammeltoft, Steen et al. (2004) Activation of p90 Rsk1 is sufficient for differentiation of PC12 cells. Mol Cell Biol 24:10573-83
Eyers, Patrick A; Maller, James L (2004) Regulation of Xenopus Aurora A activation by TPX2. J Biol Chem 279:9008-15
Tunquist, Brian J; Maller, James L (2003) Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs. Genes Dev 17:683-710
Tunquist, Brian J; Eyers, Patrick A; Chen, Lin G et al. (2003) Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest. J Cell Biol 163:1231-42
Eyers, Patrick A; Erikson, Eleanor; Chen, Lin G et al. (2003) A novel mechanism for activation of the protein kinase Aurora A. Curr Biol 13:691-7
Tunquist, Brian J; Schwab, Markus S; Chen, Lin G et al. (2002) The spindle checkpoint kinase bub1 and cyclin e/cdk2 both contribute to the establishment of meiotic metaphase arrest by cytostatic factor. Curr Biol 12:1027-33
Maller, James L; Schwab, Markus S; Gross, Stefan D et al. (2002) The mechanism of CSF arrest in vertebrate oocytes. Mol Cell Endocrinol 187:173-8
Qian, Y W; Erikson, E; Taieb, F E et al. (2001) The polo-like kinase Plx1 is required for activation of the phosphatase Cdc25C and cyclin B-Cdc2 in Xenopus oocytes. Mol Biol Cell 12:1791-9
Schwab, M S; Roberts, B T; Gross, S D et al. (2001) Bub1 is activated by the protein kinase p90(Rsk) during Xenopus oocyte maturation. Curr Biol 11:141-50
Maller, J L; Schwab, M S; Roberts, B T et al. (2001) The pathway of MAP kinase mediation of CSF arrest in Xenopus oocytes. Biol Cell 93:27-33

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